Structural insights into modulation and selectivity of transsynaptic neurexin–LRRTM interaction

Atsushi Yamagata; Sakurako Goto-Ito; Yusuke Sato; Tomoko Shiroshima; Asami Maeda; Masahiko Watanabe; Takashi Saitoh; Katsumi Maenaka; Tohru Terada; Tomoyuki Yoshida; Takeshi Uemura; Shuya Fukai

doi:10.1038/s41467-018-06333-8

Structural insights into modulation and selectivity of transsynaptic neurexin–LRRTM interaction

Atsushi Yamagata, Sakurako Goto-Ito, Yusuke Sato, Tomoko Shiroshima, Asami Maeda, Masahiko Watanabe, Takashi Saitoh, Katsumi Maenaka, Tohru Terada, Tomoyuki Yoshida, Takeshi Uemura, Shuya Fukai^*

^*Corresponding author for this work

Molecular Neuroscience

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1β–LRRTM2 complex at 3.4 Å resolution. The Nrxn1β–LRRTM2 interface involves Ca²⁺-mediated interactions and overlaps with the Nrxn–neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn.

Original language	English
Article number	3964
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06333-8
State	Published - 2018/12/01

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Structural insights into modulation and selectivity of transsynaptic neurexin–LRRTM interaction",

abstract = "Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1β–LRRTM2 complex at 3.4 {\AA} resolution. The Nrxn1β–LRRTM2 interface involves Ca2+-mediated interactions and overlaps with the Nrxn–neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn.",

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AU - Yamagata, Atsushi

AU - Goto-Ito, Sakurako

AU - Sato, Yusuke

AU - Shiroshima, Tomoko

AU - Maeda, Asami

AU - Watanabe, Masahiko

AU - Saitoh, Takashi

AU - Maenaka, Katsumi

AU - Terada, Tohru

AU - Yoshida, Tomoyuki

AU - Uemura, Takeshi

AU - Fukai, Shuya

PY - 2018/12/1

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N2 - Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1β–LRRTM2 complex at 3.4 Å resolution. The Nrxn1β–LRRTM2 interface involves Ca2+-mediated interactions and overlaps with the Nrxn–neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn.

AB - Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1β–LRRTM2 complex at 3.4 Å resolution. The Nrxn1β–LRRTM2 interface involves Ca2+-mediated interactions and overlaps with the Nrxn–neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn.

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JO - Nature Communications

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Structural insights into modulation and selectivity of transsynaptic neurexin–LRRTM interaction

Abstract

ASJC Scopus subject areas

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